Purpose: The study which we have now completed was a single, randomized clinical trial of exercise and weight management with three long term objectives. The first was to evaluate the efficacy of two behavioral interventions--aerobic exercise and weight management--in reducing blood pressure (BP) in people with mild HTN; the second was to examine the mechanisms by which BP was reduced; and the third was to investigate the effects of behavioral treatment on cognitive performance and related aspects of quality of life. Methods: We recruited 144 individuals with mild HTN. Individuals who were eligible but unable to participate in the intervention were initially assigned to a non-random control group (N=11). However, this practice was stopped and we are only including the 133 fully randomized subjects in our data analysis. Volunteers were randomly assigned to 6 months of exercise alone, exercise with weight management, or a control group. Subjects underwent evaluations at baseline and at 6 months, in addition to an eligibility screening--physical exam and blood and urine samples. Measurements of BP were obtained in the clinic, during ambulatory BP monitoring, and during physical exercise and mental stress testing. BPs were also obtained at 1 year follow-up. To examine potential mechanisms responsible for BP changes, subjects underwent glucose tolerance testing, lipid analysis, studies of heart rate variability, and hemodynamic and neuroendocrine assessments. Because hypertension has been shown to be associated with measurable changes in cognitive function, which may be reversible when BP is normalized, subjects also completed neuropsychological assessments along with psychometric testing. Finally, the clinical significance of the BP changes were determined by repeat cardiac echocardiography, as well as by repeated BP testing at baseline, 6 months, and 1 year follow-up. Results: Results indicate that while exercise alone is effective in reducing both systolic and diastolic blood pressure, the addition of a behavioral weight loss program augments significantly the efficacy of exercise alone. The magnitude of the resting clinic blood pressure reductions were 4-5 mm in the Exercise alone condition, but increased to 5-8 mm in the combined exercise and weight loss condition. Larger BP reductions also were observed for the combined condition relative to exercise alone with ambulatory blood pressure monitoring during routine activities of daily living, particularly for DBP, and during mental stress testing in the laboratory setting. In terms of potential mechanisms that may be responsible for the BP changes, changes in glucose metabolism and increased vagal tone were associated with BP reductions. Exercise alone was not associated with significant weight loss or changes in body composition. In addition exercise alone did not improve insulin sensitivity (as assessed indirectly by fasting plasma insulin), insulin secretory response, or plasma glucose. While the FPG in the present sample of hypertensive patients was normal, they did demonstrate substantial insulin resistance, as indicated by the presence of fasting and post prandial hyperinsulinemia. Consistent with this other research, the present findings did not show a substantial effect of exercise alone on glucose or insulin parameters unless the exercise was combined with diet. It would appear that a weight loss, over and above exercise alone, is necessary to induce favorable metabolic changes. Increased heart rate variability was also associated with exercise training, particularly among patients who also lost weight. Aerobic endurance training was associated with an increase in mean R-R interval (bradycardia) at rest and that this bradycardia was accompanied by an increase in the standard deviation of R-R interval. This improvement was even greater among patients who lost weight in the Combination group. In contrast to findings from other studies, no treatment effects were observed for lipids or catecholamines in this project. Significance: Hypertension (HTN) is a major health problem in the U.S. placing some 58 million Americans at increased risk for stroke, myocardial infarction, kidney failure, and peripheral vascular disease. The information obtained from this study will have important practical significance by determining the efficacy of exercise and weight reduction in lowering BP in men and women with mild hypertension, and by assessing the clinical importance of these changes.